title: Proteomic study of the toxic effect of oligomeric Aβ1-42 in situ prepared from 'iso-Aβ1-42'.
abstract: Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders even so the exact pathomechanism is still unclear. Recently, it is widely accepted that amyloid-beta peptide (Aβ) toxicity is positively linked to Aβ oligomers, which may be responsible for the initiation of AD. For this reason, AD research requires well defined aggregation state and structure of Aβ. Precursor peptide 'iso-Aβ1-42' makes it possible to use Aβ1-42 with well- defined aggregation state for in vitro and in vivo experiments. The aim of this study was to identify protein expression changes from differentiated SH-SY5Y neuroblastoma cells after treatment with oligomeric Aβ1-42 prepared in situ from 'iso-Aβ1-42'. In our experiment, a cell viability assay revealed a strong and time-dependent toxic effect of oligomeric Aβ1-42 which was supported by dramatic morphological changes. Our proteomics study also revealed numerous significant protein expression changes (22 proteins down- and 25 proteins up-regulated) after comparison of the untreated and Aβ1-42-treated cell lysates by two-dimensional electrophoresis. From the functional classification of the identified proteins, we found deregulations of proteins involved in metabolic processes, cytoskeleton organisation and protein biosynthesis and a huge number of up-regulated stress proteins displayed oligomeric Aβ1-42-induced cell stress.
authors.affiliation: Department of Medical Chemistry, University of Szeged, Szeged, Hungary. foldi@dnt.u-szeged.hu
authors.forename: István
authors.initials: I
authors.lastname: Földi
authors.forename: Zsolt L
authors.initials: ZL
authors.lastname: Datki
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szabó
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bozsó
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: Tamás
authors.initials: T
authors.lastname: Janáky
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000633:toxicity*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007536:Isomerism; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000145:classification; D020652:Peptide Elongation Factor 2 / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000633:toxicity*; D040901:Proteomics
chemical_list: D016229:Amyloid beta-Peptides; D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D020652:Peptide Elongation Factor 2; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)